Although definition and mechanistic understanding of pro-angiogenic progenitor cells remains unsatisfactory, general agreement highlights their role in regenerative process following tissue injury and ischemia. Furthermore, stem-cell based therapy represents a hot topic of cardiovascular medicine. Recent studies provide new insights on the signalling pathways that modulate stem/progenitor cell mobilization from bone marrow, homing to ischemic area and participation in vascular remodelling and tissue healing. This review focuses on current knowledge and emerging concepts on stem cell/progenitor cell trafficking in relation to changes in surrounding environment and epigenetic modifications caused by risk factors and comorbidities.