Travel health providers are often confronted with complex scenarios when advising travelers on malaria prevention. Current challenges in prevention include malaria risk assessment, where a detailed itinerary and knowledge of malaria epidemiology are needed. Up-to-date information on the correct use, limitations, and drug interactions of current priority chemoprophylaxis agents (atovaquone/proguanil, mefloquine, doxycycline) is key. Another challenge is to identify and reach travelers who are most at risk of malaria, such as the traveler visiting friends and relatives. Posttravel, delays in presentation, diagnosis, and inappropriate treatment of malaria are key risk factors leading to death. Treatment of malaria is an emergency requiring expert in-patient management and referral to a center with adequate expertise. Artemisinin combination therapies are the drugs of choice for uncomplicated malaria. Complicated malaria is treated preferably with intravenous artesunate, and the supply and quality of this life-saving antimalarial in some settings can pose one of the most urgent challenges in travelers' malaria.