Macropinocytosis defines a series of events initiated by extensive plasma 
membrane reorganization or ruffling to form an external macropinocytic structure 
that is then enclosed and internalized. The process is constitutive in some 
organisms and cell types but in others it is only pronounced after growth factor 
stimulation. Internalized macropinosomes share many features with phagosomes and 
both are distinguished from other forms of pinocytic vesicles by their large 
size, morphological heterogeneity and lack of coat structures. A paucity of 
information is available on other distinguishing features for macropinocytosis 
such as specific marker proteins and drugs that interfere with its mechanism 
over other endocytic processes. This has hampered efforts to characterize the 
dynamics of this pathway and to identify regulatory proteins that are expressed 
in order to allow it to proceed. Upon internalization, macropinosomes acquire 
regulatory proteins common to other endocytic pathways, suggesting that their 
identities as unique structures are short-lived. There is however less consensus 
regarding the overall fate of the macropinosome cargo or its limiting membrane 
and processes such as fusion, tubulation, recycling and regulated exocytosis 
have all been implicated in shaping the macropinosome and directing cargo 
traffic. Macropinocytosis has also been implicated in the internalization of 
cell penetrating peptides that are of significant interest to researchers aiming 
to utilize their translocation abilities to deliver therapeutic entities such as 
genes and proteins into cells. This review focuses on recent findings on the 
regulation of macropinocytosis, the intracellular fate of the macropinosome and 
discusses evidence for the role of this pathway as a mechanism of entry for cell 
penetrating peptides.