Neuroinfectious diseases continue to have a profound public health impact, particularly in resource-limited settings. Here we summarize the new research into pathophysiology, diagnosis, and treatment modalities for some of the most frequent and lethal infections affecting the central nervous system, including tuberculosis, malaria, and arboviral infections. Implementation of clinical trials targeting neuroinfectious diseases in resource-limited settings has unique challenges not found when identical research is performed in resource-rich areas. Travel, communications, and technology have improved the mobility of populations worldwide. Immigration and increased international travel make it likely that clinicians worldwide will see patients affected by infectious diseases such as malaria, tuberculosis, zika, dengue, chikungunya, and Ebola. Such infections may have devastating consequences for both the individual and the society, particularly if clinicians are not familiar with disease presentation and treatment.