How do commercial pilots send distress signals?
There are three common ways to send a distress signal (roughly in order of preference):


Over the radio, to whoever you are currently talking to.
Key the microphone and announce to the world Mayday, Mayday, Mayday, the flight's callsign, and a description of the emergency. This is generally the way an emergency is declared, particularly for commercial (airline) service, as they're generally always in contact with an ATC facility
Over the radio, to anyone monitoring the "emergency" frequency.
The VHF frequency 121.5MHz is reserved for aircraft emergency communication. It is monitored at most air traffic control facilities, as well as by many airliners and other pilots with multiple radios in their aircraft. If you're not able to make contact with the facility you're currently talking to in (1) above (or if you're not currently talking to an ATC facility).
Using the aircraft's transponder.
Three transponder codes are reserved for unusual/emergency situations:
7700 for general emergencies
7600 for loss of communication (radio failure)
7500 for hijacking or other unlawful interference
All of these transponder codes alter the way the aircraft's radar target is displayed, to alert the controller to the possible problem (exactly how the display is modified depends on the radar equipment the controller has, and can range from additional text in the data block, like RDOF (RaDiO Failure) for code 7600 to changing the color of the displayed block on newer systems.
Bret detailed some of the procedures around these codes in his answer, and more information is available from the FAA, though you'll have to dig through a few referenced documents to put it all together.




Note that sometimes the order of preference changes - For example if a pilot is being threatened by a hijacker they may quietly set their transponder code to 7500 without saying anything on the radio to alert the hijacker.