Numerous studies have shown that a reduction in the endogenous functional β-cell mass is a major cause of every form of diabetes. Therefore, the development of therapies to preserve and regenerate endogenous β-cell mass and function holds great promise for both Type 1 and Type 2 diabetes. The importance of understanding the mechanisms and signaling pathways regulating beta cell death is key in our ability to prolong beta cell survival in the future. One potential way to protect beta cells would be to use growth factors that can enhance their survival against different damaging insults. In this review, we describe the current knowledge on the effects of several beta cell growth factors that have been shown to increase beta cell survival in vitro and/or in vivo against varied cell death inducers. Understanding the mechanisms that mediate the pro-survival effects of these factors will enhance the potential to use these factors, or develop drugs that target their downstream pathways, as therapeutic agents for improved beta cell survival ex vivo or in vivo in the future.