Middle Rhine Valley
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The Rhine Valley or Middle Rhine (German Mittelrhein) is the most famous section of the Rhine, running between the cities of Bonn and Bingen near Mainz in Germany and spanning the states of North Rhine-Westphalia, Rhineland-Palatinate and Hesse. The section from Koblenz to Bingen and Rüdesheim, known as the Rhine Gorge, is a UNESCO World Heritage Site, and the entire valley is often called "The Romantic Rhine".
Notable points along the river, in order from north to south:
The Rhine Valley, where the Rhine carves its way through steep hills topped with countless castles and ruins, is one of the most famous and most heavily touristed parts of Germany. Traveling here is very easy — cruises, castles and winery tours by day, sampling the wine at night — and it's no surprise that the visiting demographic is slanted heavily towards retirees looking for an easy break.
When to go
The peak season is definitely summer, when the hillsides are green and the cruise boats busy. In September, many inns and restaurants already start closing down for the winter, and almost all cruises end by November, starting up again in April.
By plane or train
The most common starting points for a tour of the Rhine Valley are Cologne, just north of Bonn, and Frankfurt, just east of Rüdesheim. Frankfurt is actually on the Main, not the Rhine itself, so the Rhine towns of Mainz and Wiesbaden also make popular starting points.
A large number of luxury cruise operators sail up (and down) the Rhine from Amsterdam to eg. Basel, Zurich or Strasbourg. The leisurely journey with plenty of stopovers typically takes anywhere from one to two weeks, with accommodation on the boat itself. Large operators include Avalon , Viking  and AmaWaterways  with low-season prices for a 7-night cruise starting from around US$2,000.
The Rheinland-Pfalz-Ticket  lets groups of up to five people travel freely for a day (9 AM onwards on weekdays, all days weekends, up to 3 AM of the following day) by train, bus and local transport within the state of Rhineland-Palatinate and Wiesbaden for €21 for a single person, €25 for two person and €37 for five person. In addition to the core stretch along the Rhine (Remagen-Oberwesel inclusive) and the train line along the Mosel, the ticket also covers a few handy train stretches outside state boundaries, notably Rolandseck-Bonn and Koblenz-Rüdesheim-Wiesbaden-Mainz.
There are not one but two train lines running along this section of the Rhine. The scenic Linke Rheinstrecke ("Left Rhine Line") runs along the left (west) bank of the river from Cologne to Mainz, while the Rechte Rheinstrecke ("Right Rhine Line") runs along the right (east) bank of the river from Cologne to Wiesbaden. The Linke side, generally considered the more scenic of the two, is more heavily trafficked and has InterCity services, while the Rechte side is mostly dedicated to cargo and is limited to regional passenger trains running less than once per hour. Interchanging between the two is possible at Koblenz; the city is on the left, but some trains running on the Rechte start or terminate in there.
Beware that, if you're buying individual tickets, train zones get confusing and pricy fast. While the "core" of the Rhine Valley is in Rhineland-Pfalz's VRM tariff zone, the Rheingau stretch east of Lorch is also in Frankfurt's RMV zone, while going north of Remagen passes into Cologne's VRS area.
The Köln-Düsseldorfer Rheinschiffahrt , better known as KD, runs cruises and scheduled services up and down the river between Cologne and Mainz. The summer season (May-Sept) sees up to 8 services daily on the busiest parts of the river, but services are cut considerably in the shoulder seasons of April and October and slow down to a trickle in the winter. Traveling end to end takes over 11 hours (€49 one way), so most travellers opt for much smaller segments: St. Goar to Bingen, for example, passes by the famous rock of Loreley, takes about 90 minutes and costs €15.30.
While KD has the most extensive network and schedules, there is quite a bit of competition. For example, Bingen-Rudesheimer  operates scheduled services on the south half between Rüdesheim and St. Goar.
The Rhine Valley is famous for wine, and this section of the Rhine along with its tributaries the Mosel and Nahe cover 5 of Germany's 13 officially recognized wine regions. From north to south:
Wear clothes that are suitable for the weather. If you go in April through August wear some summer/spring clothes. If its September through March pack your coats up!