Get rid of many a restless desire (5)
I believe the answer is:
ditch
'get rid' is the definition.
(I've seen this before)
'many a restless desire' is the wordplay.
'many' becomes 'D' (Roman numeral for 500).
'a restless desire' becomes 'itch' (as in having an itch for something).
'd'+'itch'='DITCH'
'of' acts as a link.
(Other definitions for ditch that I've seen before include "Land in water" , "give up" , "Dump (informal)" , "Gully or furrow" , "long depression" .)