Many therapeutic agents have intracellular compartments as their site of action. Targeted delivery of these agents to their specific intracellular targets could result in enhanced therapeutic efficacy and reduced toxicity. Various carriers have been shown useful in targeted delivery of different classes of therapeutic agents. Among these carriers, biodegradable nanoparticles formulated from biocompatible polymers poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) have shown the potential for sustained intracellular delivery of different therapeutic agents. In this review, we discuss different intracellular targets, barriers to intracellular delivery, mechanism and pathways of intracellular delivery, and various carriers and approaches that have been investigated for intracellular drug delivery.