Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted by disease, particularly cancer. To carry out their well established roles such as phagocytic clearance of dying cells as well as their tissue-specific functions, macrophages must be able to move into and through tissues. In cancers, this interstitial migratory ability of macrophages is used by tumour cells to help them escape and disseminate from the primary tumour. Macrophage migration is stimulated by the growth factor, colony-stimulating factor-1 (CSF-1), which also regulates macrophage survival, proliferation and differentiation. Mutational analysis of CSF-1 receptor signalling indicates that the major mediators of CSF-1-induced motility are 1) phosphatidylinositol-3 kinase (PI3K) via its association with the activated CSF-1R at pY721, and 2) the Src family kinases (SFKs). Macrophages express isoforms of both PI3K and SFKs that can be targeted to specifically inhibit macrophage motility. Recent work in my lab indicates that selective inhibition of either PI3K p110δ or Hck blocks macrophage migration and tumour cell invasion both in vitro in our macrophage/tumour cell mammosphere co-cultures and in vivo using an orthotopic mouse mammary tumour model.