The main protozoan parasites, including Plasmodium, Leishmania, Toxoplasma, and Trypanosoma, face significant environmental stress during their life cycles. To survive, they rely on heat shock proteins (Hsps), which play essential roles in protein folding, preventing aggregation, and stabilizing cellular pathways under stress. Due to their critical functions, parasite Hsps have emerged as promising drug targets and potential diagnostic biomarkers. Several studies have revealed structural and functional differences between parasite and human Hsps, making them attractive for selective drug targeting. However, challenges such as specificity and host toxicity remain obstacles in Hsp-targeted therapies. Additionally, several key questions remain unanswered: What unique adaptations allow parasite Hsps to function efficiently? How do they interact with other chaperone systems? What roles do they play in parasite virulence and host-pathogen interactions? Addressing these gaps will enhance our understanding of parasite biology and support the development of more effective therapeutic and diagnostic strategies. This review evaluates the current knowledge on parasite Hsps, their potential as drug targets, and approaches to overcome existing challenges. Gaining deeper insights into their mechanistic roles could lead to safer and more targeted interventions against protozoan infections.