In On the Road, restlessness and the resulting motion are tied up with the madness of the Beat Generation. The need to move comes from dissatisfaction. Most interesting is motion through time vs. motion through space, as Dean focuses on the former while Sal the latter. The motion becomes futile, however, as there is no true heaven at the end of their traveling. Restlessness is also tied to the characters romantic relationships, as they feel the same dissatisfaction with women, and the same need for more and more variety.
Sal’s geographical restlessness mirrors his sexual restlessness, suggesting that there is no "end of the road" for either.