Cassava or manioc (Manihot esculenta Crantz), a perennial shrub of the New World, currently is the sixth world food crop for more than 500 million people in tropical and sub-tropical Africa, Asia and Latin America. It is cultivated mainly by resource-limited small farmers for its starchy roots, which are used as human food either fresh when low in cyanogens or in many processed forms and products, mostly starch, flour, and for animal feed. Because of its inherent tolerance to stressful environments, where other food crops would fail, it is often considered a food-security source against famine, requiring minimal care. Under optimal environmental conditions, it compares favorably in production of energy with most other major staple food crops due to its high yield potential. Recent research at the Centro Internacional de Agricultura Tropical (CIAT) in Colombia has demonstrated the ability of cassava to assimilate carbon at very high rates under high levels of humidity, temperature and solar radiation, which correlates with productivity across all environments whether dry or humid. When grown on very poor soils under prolonged drought for more than 6 months, the crop reduce both its leaf canopy and transpiration water loss, but its attached leaves remain photosynthetically active, though at greatly reduced rates. The main physiological mechanism underlying such a remarkable tolerance to drought was rapid stomatal closure under both atmospheric and edaphic water stress, protecting the leaf against dehydration while the plant depletes available soil water slowly during long dry periods. This drought tolerance mechanism leads to high crop water use efficiency values. Although the cassava fine root system is sparse, compared to other crops, it can penetrate below 2m soil, thus enabling the crop to exploit deep water if available. Leaves of cassava and wild Manihot possess elevated activities of the C4 enzyme PEP carboxylase but lack the leaf Kranz anatomy typical of C4 species, pointing to the need for further research on cultivated and wild Manihot to further improve its photosynthetic potential and yield, particularly under stressful environments. Moreover, a wide range in values of Km (CO2) for the C3 photosynthetic enzyme Rubisco was found among cassava cultivars indicating the possibility of selection for higher affinity to CO2, and consequently higher leaf photosynthesis. Several plant traits that may be of value in crop breeding and improvement have been identified, such as an extensive fine root system, long leaf life, strong root sink and high leaf photosynthesis. Selection of parental materials for tolerance to drought and infertile soils under representative field conditions have resulted in developing improved cultivars that have high yields in favorable environments while producing reasonable and stable yields under stress.