By ship
With the Erie Canal, Genesee River, Lake Ontario, and Irondequoit Bay, waterways are a rare but not unheard-of method of getting to Rochester. Your best bets for mooring are at the mouth of the Genesee the Rochester harbor and in Irondequoit Bay, but those only work if you're coming from Lake Ontario. If you're on the Erie Canal coming from points east or west, you can often moor in one of the villages along the way, including Pittsford, Fairport, and Brockport, although these are all a few miles outside of Rochester. You could also take the canal to the river, then north almost to downtown, mooring at Brooks Landing or Corn Hill Landing.
By train
The Amtrak station, 320 Central Ave Inner Loop to N Clinton Ave, quick right onto Central, (http://www.amtrak.com/ser...), has daily scheduled service on three lines. The Empire Service heads east to Syracuse, Albany, and New York City with some stops along the way, and west to Buffalo and Niagara Falls. The Maple Leaf is the same but keeps going past Niagara Falls across the Canadian border to Toronto. The Lake Shore Limited from Chicago to Boston or New York also stops in Rochester.
The station is not in the "best" part of town, so don't try to walk there at night. The station itself, and its parking lot, are well lit and quite safe, though. Be prepared for delays—this is Amtrak after all—and be aware there's really nothing to do to kill time in or around the station.
A few taxis will often be waiting at the station around the scheduled arrival times, or you may want to arrange for a rental agency to pick you up.
By car
Because of Rochester's location close to Lake Ontario, the New York State Thruway, Interstate 90, passes a few miles to the south, through the southern suburbs. It still provides the quickest route into the area from the east and west, though. Whichever way you're coming, you'll take I-490 to get into the city proper; it leaves the Thruway eastbound at Exit 47, passes through downtown Rochester, then rejoins the Thruway at Exit 45.
Exit 46, between them, is for I-390, the primary route into Rochester from points south. I-390's south end is at I-86, and it also connects with U.S. Route 15 out of Pennsylvania.
From the northeast, if you don't want to head south to the Thruway, most drivers will take State Route 104, a former federal route that constitutes the main rural drag through the northern part of Western New York. 104 also works if you're coming from the northwest—the northern part of the Niagara Frontier—but an alternative is the Lake Ontario State Parkway, which starts 35 miles northwest of downtown and follows the lake shore to the Rochester harbor.