Cell therapy using mesenchymal stromal cells (MSCs) is a promising new avenue of treatment for critical limb ischemia (CLI). Preclinical studies have suggested that MSCs enhance neovascularization in ischemic limbs. In this commentary, we discuss a recent study by Gupta and colleagues, one of the first human trials using allogeneic MSCs for CLI, in relation to the current state of knowledge regarding cell therapy for CLI.