Prague's climate is continental, so in summer plan on relatively warm days and cool nights. Spring tends to be wet and cool; fall is drier but also on the chilly side. In winter, pack plenty of warm clothes and plan to use them. An umbrella is a good idea any time of year. Note that areas in higher elevations tend to stay very cool even in midsummer.
In general, pack for comfort rather than for style. Casual dress is the norm for everyday wear, including at most restaurants. Men will need a sport coat for an evening out at a concert or the opera. Shorts for men are not as common in Prague as they are in North America. In the evening, long pants are the norm, even in summer.
Many areas are best seen on foot, so take a pair of sturdy walking shoes and be prepared to use them. High heels can present considerable problems on the cobblestone streets of Prague.
Some items that you take for granted at home are occasionally unavailable or of questionable quality in Eastern and Central Europe, though the situation has been steadily improving. Toiletries and personal-hygiene products are relatively easy to find, but it's always a good idea to bring necessities when traveling in outlying areas, especially on weekends.