Pumilio and FBF (PUF) proteins are conserved stem cell regulators that maintain germline stem cells (GSCs) in worms and flies. Moreover, they are also present in vertebrate stem cells. The nematode Caenorhabditis elegans has multiple PUF proteins with specialized roles. Among them, PUF-8 protein controls multiple cellular processes, including proliferation, differentiation, sperm-oocyte decision, and cell fate reprogramming, depending on the genetic context in the C. elegans germline. In this review, we describe the possible mechanisms of how PUF-8 protein systematically controls multiple cellular processes in the C. elegans germline. Since PUF proteins are evolutionarily conserved, we suggest that a similar mechanism may be involved in controlling stem cell regulation and differentiation in other organisms, including humans.