The Lower East Side (or simply LES) is a center of all things cool: arts and nightlife, restaurants and cafés, boutiques and salons. What was once the "Gateway to America"—and home to waves of Irish, German, Jewish, Hispanic, and Chinese immigrants—is now a quickly gentrifying neighborhood where modern high-rises, the ultracontemporary New Museum, and low-key hangouts all exist in the same corner of Manhattan.
Ludlow Street and Orchard Street in particular are great for exploring the boutiques and galleries wedged between bars and small restaurants. On Friday and Saturday nights, be aware that the neighborhood scene can be as raucous as in a college town, especially on Rivington and Orchard Streets.
The best time to experience the neighborhood's past is by day. The excellent Lower East Side Tenement Museum movingly captures the immigrant legacy of tough times and survival instincts. You might not find many pickles being sold from barrels anymore, but this remains a good place to nosh on delicious Jewish food like matzo-ball soup, corned beef, and knishes from Katz's Delicatessen or Russ & Daughters.