During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling event evolved to cell death. It plays a pivotal role in several immunological reactions in particular deletion of autoreactive immune cells. Helminth-triggered apoptosis in immune cells exhausts host immunity, which paves the way for generating a permissive environment and chronic infection. This review provides a compilation of recent investigations discussing the apoptotic mechanisms exploited by different worms and the immunological consequences of immune cell death. Finally, the anti-cancer effects of some worm-derived molecules due to their apoptotic effects are discussed, highlighting as potentially druggable candidates to combat cancer.