Malaria is a medical emergency that claims the lives of about 20 people each year in France. Adult and pediatric emergency departments are on the front lines for diagnosing the disease and assessing the severity of cases, which determines the choice of initial treatment and the final decision regarding patient management (outpatient care, admission to medical wards, or admission to intensive care). Integrating the patient, upon discharge from the emergency department, into a care pathway tailored to their clinical condition and personal and social context is essential to the quality of care and patient safety. However, the proper organization of the patient’s clinical pathway within the emergency department is also essential. Here we present a review of the main diagnostic and therapeutic challenges of malaria, as well as diagnostic and therapeutic decision-making tools to be implemented in emergency departments to improve the quality and safety of patient care.