Is there a dedicated emergency frequency?
If a pilot is already speaking to ATC (or monitoring a frequency) they should continue to use that frequency for any emergency or abnormal situation.
If they are not currently receiving ATC services or on an ATC frequency, attempt to use 121.5. Many ATC providers and enroute airliners monitor this frequency and can relay or provide assistance.
The FAA's AIM (6-3-1) describes emergency use of 121.5 in the United States:

h. Although the frequency in use or other frequencies assigned by ATC are preferable, the following emergency frequencies can be used for distress or urgency communications, if necessary or desirable:

1. 121.5 MHz and 243.0 MHz. Both have a range generally limited to line of sight. 121.5 MHz is guarded by direction finding stations and some military and civil aircraft. 243.0 MHz is guarded by military aircraft. Both 121.5 MHz and 243.0 MHz are guarded by military towers, most civil towers, FSSs, and radar facilities. Normally ARTCC emergency frequency capability does not extend to radar coverage limits. [emphasis mine] If an ARTCC does not respond when called on 121.5 MHz or 243.0 MHz, call the nearest tower or FSS.