Sleeping sickness or Human African Trypanosomiasis (HAT) is endemic in 36 African countries and around 60 million people are at risk of being infected. HAT is transmitted by the Tsetse fly and is fatal without treatment. Up to 2009, existing treatments for stage 2 of the disease were toxic or difficult to administer. In 2009, DNDi and its partners have launched the first new treatment for HAT in 25 years.

Leishmanisais occurs in 98 countries with 350 million people living at risk worldwide. The parasite that leads to infection is called Leishmania and transmitted by sandflies. Leishmaniasis is a poverty-associated disease with several different forms, of which visceral leismaniasis, fatal without treatment, and cutaneous leshmaniasis are the most common. Existing treatments are difficult to administer, toxic, and costly. Drug resistance is also an increasing problem

Chagas disease is endemic in 21 countries across Latin America and kills more people in the region than any other parasite-borne disease, including malaria. In total, 100 million people are at risk worldwide and patient numbers are growing in non-endemic countries such as the United States, Australia, and Europe. The disease is transmitted by an insect known as the "kissing bug" and without treatment, is potentially fatal. Existing treatments have an unsatisfactory cure rate and can have toxic side effects.

Malaria kills one child every 30 seconds in sub-Saharan Africa and is the leading parasitic cause of morbidity and mortality worldwide. 3.2 billion people are at risk and while effective treatments exist, they have important limitations, including widespread drug resistance. DNDi and its partners have already developed two inexpensive, efficacious, field-adapted treatments.

In 2011, DNDi started taking on specific projects for two new disease areas:

There are currently 33.3 million people living with HIV/AIDS worldwide, of which 97% are in low- and middle-income countries. This figure includes 2.5 million children below 15 years of age; the overwhelming majority of whom live in sub-Saharan Africa. Infants acquire the virus before, during, or after birth, and without access to treatment half of them will die before their second birthday.

Filarial diseases, onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) inflict the heaviest socioeconomic burden of all the neglected tropical diseases and affect millions in poverty-stricken areas. Current treatments for these diseases cannot be used for patients who are infected with a related nematode worm, Loa loa, because of the severe side effects caused by rapid killing of juvenile Loa loa worms. There is an urgent need for a new treatment for onchocerciasis and lymphatic filariasis in Loa loa endemic regions.