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Tropical malaria caused by the protozoan Plasmodium falciparum is responsible for more than 200 million clinical episodes and at least 660,000 human deaths annually. Parasite resistance increases continuously against the presently available drugs. To further understand the biochemical pathways involved in the mechanisms of drug resistance, a quantitative proteomic approach has been developed using stable isotope labeling by amino acids in cell culture (SILAC). In contrast to previous studies with higher drug concentrations, three different sub-lethal dosage amounts of chloroquine were used to treat parasite cultures. The protein abundance was quantified and a list of proteins and their related pathways was collected. Programmed Cell Death (Apoptosis) is one of the control mechanisms used by higher multicellular animals that are crucial for the continuing development of the surviving cells. Surprisingly the causative agent of malaria, a protozoan parasite, shows signs of this programmed “suicide”. DNA fragmentation assays and morphological characterization have been carried out under similar sub-lethal drug concentrations conditions as the proteome samples pointing to an apoptotic phenotype. The proteomic data point to some of the players that might be involved. An up-regulation of cytochrome C suggests it is a protein involved in the apoptosis pathway. We hypothesize that cytochrome C is involved in a pathway similar to the one found in another unicellular organism, yeast, where after binding a target protein a proteolytic cascade is turned on. In order to test this working hypothesis an assay was developed to confirm the involvement of cytochrome C in proteolysis of downstream targets using a fluorogenic substrate.