Malaria is the most important parasitic disease of humans accounting for high morbidity and mortality rates in the tropical and subtropical countries of Africa, Asia, and the Americas. Combination chemotherapy is recommended for treatment of acute uncomplicated malaria as a result of widespread drug resistance. Tuberculosis (Tb) is also widespread and combination therapy is its standard of care. Treatment of malaria in an individual on antituberculosis drugs requires dexterity in order to avoid adverse drug interactions as, for example, rifampicin and/or isoniazid-induced liver injury may be worsened by an amodiaquine-containing artemisinin-based combination therapy with dire consequences. Interestingly, rifampicin has antiplasmodial activity, enhancing, for example, the antimalarial effect of quinine. The artemisinin-based combination therapy (ACT)-anti-Tb drugs’ pharmacokinetic interactions may also reduce exposure to mainly the former, as a result of induction of metabolism of the object drug and/or increased efflux by membrane-bound transporter proteins. This chapter discusses antimalarial-anti-Tb drug interactions, paying particular attention to commonly used ACTs in sub-Saharan Africa, where both conditions are rampant.