The main language spoken is, not surprisingly, Czech. The Slovak language can also be often heard, as there is a sizable Slovak minority and both languages are mutually intelligible. Czech people are very proud of their language, and thus, even in Prague you will not find many signs written in English (outside of the main tourist areas). Many older people, especially outside the large cities, are also unable to converse in English, so it's good to learn some Czech or Slovak before your arrival. However, most young people speak at least some English, as it has been taught in most schools since 1990.
Most Czechs speak a second and often a third language. English is the most widely known, especially among younger people. German is probably the most widely spoken second language among older people. Russian was taught very extensively under communist rule, so most people born before c. 1975 speak at least some Russian (and often pretty well). However the connection with the communist era and the Soviet led invasion in 1968 (as well as today's Russian-speaking criminal gangs) has given this language some negative connotations. It is also not very useful with younger people, as it is not, despite the common misconception, mutually intelligible with Czech (beyond some similar words and simple sentences). Other languages, like French or Spanish, are also taught in some schools, but you should not count on it. People may also understand some basic words or simple sentences in other Slavic languages (Polish, Serbo-Croatian, etc).
The Czech and Slovak languages are very difficult for English-speakers to grasp, as they, like their sisters, can be tongue-twisting languages to learn (especially Czech) and take time and practice to master, especially if you're not really familiar with the other Slavic languages, including Russian. However, if you can learn the alphabet (and the corresponding letters with accents), then pronunciation is easy as it is always the same - Czechs and Slovaks pronounce every letter of a word, with the stress falling on the first syllable. The combination of consonants in some words may seem mind-bogglingly hard, but it is worth the effort!
The Czech language has many local dialects, especially in Moravia. Some dialects are so different that they can be sometimes misunderstood even by a native Czech speaker from a different region. However all Czech people understand the standard Czech (as spoken in TV, written in newspapers and taught in schools) and should be able to speak it (but some are too proud to stop using their local dialect). Some of them are even unable to speak standard Czech but write it correctly.
Czechs have different writing style, and the Slovak language is softer. The vocabulary is similar, with occasional words not understood. The younger generation born after the dissolvent of Czechoslovakia are growing apart and have problems to understand each other.
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