Drought and heat stresses are key limiting factors for wheat production in Central and West Asia and North Africa (CWANA) and sub Saharan Africa (SSA) regions. The wheat breeding program at ICARDA applies both conventional and molecular breeding approaches to develop high yielding wheat genotypes with resistance to major abiotic and biotic stresses using inter-country shuttle breeding and key locations yield testing at Terbol station in Lebanon, Sids in Egypt, Kulumsa in Ethiopia, Izmir in Turkey, Wadmedani in Sudan, and Merchouch & Sidi Al Aidi stations in Morocco. Yield levels of the top yielding elite genotypes range up to 6t/ha at Wadmedani station of Sudan under extreme heat stress, 7t/ha at Merchouch station of Morocco under terminal moisture stress (260 -300 mm), and 11 t/ha at Sids station in Egypt under optimum conditions. Genetic gain analysis from 1980 to 2017 showed 2.5, 1.3 and 2.3% year -1 increment at Merchouch, Wadmedani and Sids stations, respectively. Significant MTAs for yield under heat stress have been identified. wsnp_Ex_c12812_20324622 marker on chromosome 4A and wsnp_Ex_c2526_4715978 on chromosome 5A were significantly correlated with grain yield under heat stressed environments. Wheat genotypes carrying the cytosine base at the wsnp_Ex_c12812_20324622 and wsnp_Ex_c2526_4715978 markers out-yielded the ones carrying the alternative bases by 15% while genotypes carrying the cytosine base at only one of the two markers increased their yield by 7.9-10%, suggesting the importance of using these markers for MAS in breeding programs to increase yield under heat stress. Pedigree analysis showed that resistance sources for heat and drought tolerance in such elite germplasm were introgressed from synthetic wheats and wild relatives mainly T. dicoccoides. On an annual basis, ICARDA’s spring bread wheat program composes and distributes about 400 elite set of genotypes through international nurseries and yield trials to countries in the CWANA and SSA regions and beyond upon request for potential direct release/or parentage purposes. In the last 5 years alone, the national programs in the CWANA and SSA regions have released more than 50 spring bread wheat varieties of ICARDA origin.