Introduction Pericytes are cells with intriguing properties that have only recently attracted the attention of numerous researchers. In the past years, their function was mainly associated with microvascular homeostasis, angiogenesis and maintenance of blood-tissue barriers. Recently, several studies suggest that pericytes play a predominant role in acute as well as chronic diseases contributing to damage or tissue repair in an organ specific manner. Given their role in inflammatory and fibrotic context, the activation of pericyte Toll like Receptor-4 (TLR-4) signaling was suggested as a powerful molecular mechanism of pericytes activation and dysfunction. Here we review emerging works regarding the involvement of the TLR-4 signaling in pericytes activation both in healthy and pathological conditions.