Intracellular vesicles like lysosomes move bidirectionally and in a stop-and-go fashion along microtubules. This involves the activities of two motor types; the dynein-dynactin motor complex for inward and the kinesin motors for outward transport. We considered this transport in the context of living cells using endogenously tagged fluorescent proteins. We show how the perinuclear cloud of lysosomes is positioned and how the mobile pool of lysosomes surf on the surface of the ER while moving along microtubules. The motor proteins utilize anchors on the lysosomal membrane for binding. By quantifying the different components in this system, motor binding appears to be the limiting factor. In fact, movement is not controlled by the number of motors on a vesicle but by their activation, a process controlled by microtubule-associated proteins. The activated dynein-dynactin motor is assembled at the growing microtubule plus end and then moves inward to be intercepted by Rab7-RILP on lysosomes for lysosomal inward movement. The kinesin motor is activated at various sites along microtubules. We present a new model explaining bidirectional transport of lysosomes by considering these in the context of living cells.