Membrane type 1 matrix metalloproteinase (MT1-MMP) is a central regulator of proteolytic cell invasion and, in its surface-associated form, can cleave multiple components of the extracellular matrix. The molecular mechanisms that regulate the trafficking of MT1-MMP to and from the cell surface, therefore, are of great interest, but current knowledge is limited. Rab GTPases are of crucial importance for numerous aspects of intracellular transport, so might they impact on the trafficking of MT1-MMP? On page 2820, Stefan Linder and colleagues investigate. Using primary human macrophages, they show that RAB5A, RAB8A and RAB14, in both their endogenous and overexpressed forms, co-localise with MT1-MMP-positive vesicles. Expression of mutant constructs as well as small interfering RNA-induced knockdown of these three Rab GTPases show them to be crucial for regulating cell-surface exposure of MT1-MMP, contact of MT1-MMP-positive vesicles with podosomes, degradation of extracellular matrix at podosomes in two and three dimensions, as well as three-dimensional proteolytic invasion of macrophages. These data identify RAB5A, RAB8A and RAB14 as important regulators of MT1-MMP trafficking and invasive migration of macrophages. Because MT1-MMP is a crucial proteinase for many invasive cell types, including cancer cells, these findings could have broad translational potential.