Amongst various cellular phenomena, changes to the organisation and integrity of cytoskeletal proteins are required for vesiculation, the process of membrane microparticle (MP) shedding, to occur. As support for the biological significance of MP in regulating physiological and pathological processes increases, so does the demand for understanding the key mechanisms involved in their formation and release. This review summarises data investigating the cytoskeletal-membrane interface during vesiculation, focusing on the molecular signalling pathways that regulate actin dynamics in particular. A clear discrepancy in the literature, which is addressed in this assessment, is the distinction between mechanisms governing apoptotic bleb formation and MP release. This evaluation furthermore highlights the value of studying vesiculation from the perspective of the purified MP and intends to highlight the potential for cytoskeletal targeted therapies in modulating MP production.