Parasite redox biology is vital for understanding parasite-host interactions and adaptations. Studies in this area are leading to discoveries regarding drug targets and drug leads to treat infections caused by protozoan and worm parasites for which there are few effective drugs. Parasite unique and nonredundant core redox enzymes are choke points of metabolism and pharmacological targets. This Forum revises this concept and proposes new drug targets. It also highlights recent studies using genetically manipulated and natural strains that reveal emerging regulatory functions of antioxidant enzymes in parasite differentiation, apoptosis, virulence, acute infection, and disease progression and outcome. The challenge ahead is to understand the redox changes linked to differentiation and drastic transitions between environments that take place during parasitic complex life cycles. The combined use of new tools and techniques, such as genetically-manipulated parasites, live imaging, redox sensors, and proteomics, allow the challenge to be undertaken. Some of these methodologies, for example, transgenic parasites encoding redox biosensors, can also be applied to drug high throughput screening and to assess the effect of currently known drugs that affect redox homeostasis.