The FGF system plays a pivotal role in multiple myeloma growth and dissemination. FGF antagonists promote mitochondrial oxidative stress and apoptosis in myeloma cells by inducing proteasomal degradation of the c-Myc oncoprotein. Inhibition of the FGF system prevents the homing of grafted human myeloma cells to the bone marrow-like caudal niche of zebrafish embryos. This study provides new insights into the mechanisms by which FGF antagonists promote multiple myeloma cell death. For details, see article by Ronca and colleagues on page 2340.