We report analyses of regional trends in overall and cause-specific mortality in Belarus for the period 1990–2007. We explore the respective spatial patterns and attempt to determine the factors responsible for the regional mortality variation. The results show that inter-regional mortality differentials tend to rise, mainly because of the growing advantage of the capital over other regions. The increasing variation is associated with diverging trends in mortality from external causes of death. Mortality tends to be higher in the eastern part of the country. Regional data show that changes in mortality are largely explained by alcohol and socio-economic conditions, as measured by unemployment and poverty rates. Cardiovascular and external-cause mortality are strongly associated with alcohol and unemployment, while poverty is an important predictor of suicide and homicide mortality. Clusters of elevated mortality from certain cancers located in the contaminated zone point to the possible impact of the Chernobyl accident.