Simplified, with credit to Brett Terpstra:
It looks like the easiest way to accomplish this is to create an AppleScript that sends a command to the Skype API to answer or hang up the call. Here it is, in all its glory:
tell application "System Events" to set _proc to name of processes as list
if _proc contains "Skype" then
tell application "Skype"
set calls to send command "SEARCH ACTIVECALLS" script name "AnsweringScript"
set callID to last word of calls
if callID is not "CALLS" then
set status to send command "GET CALL " & callID & " STATUS" script name "AnsweringScript"
if last word of status is "RINGING" then
send command "ALTER CALL " & callID & " ANSWER" script name "AnsweringScript"
send command "ALTER CALL " & callID & " HANGUP" script name "AnsweringScript"
To turn that into a keyboard shortcut, save it as an application and then install FastScripts, which is a piece of software that lets you assign keyboard shortcuts to applications.