Pearl millet (Pennisetum glaucum) is an important food and cash crop for many people living in the semi arid areas of Uganda. But information about the common diseases and their effect on yield is lacking yet it is important in designing a realistic and focused pearl millet breeding programme aimed at increasing yield. A disease survey was done in 2012 in the farmers’ fields in the predominantly pearl millet growing districts of Kumi and Katakwi in eastern and Kitgum and Lamwo in northern Uganda to identify the major diseases of pearl millet and establish their incidence, severity correlation and effect on grain yield. The aim of the study therefore was to identify the major pearl millet diseases that affect production in Uganda. In terms of incidence, rust (Puccinia substriata) (73.58%) was the most frequent disease followed by ergot (Claviceps fusiformis) (62.98%), then leaf blast (Pyricularia grisea) (61.25%) and smut (Moesziomyces penicillariae) (26.76%). However, in terms of severity, leaf blast (62.20%) was the most severe followed by rust (43.33%), ergot (29.46%) and smut (14.18%). Using SPSSv20, backward model reduction regression of disease parameters against grain yield, results show disease severities of rust, ergot, leaf blast and incidences of smut and rust were the most important in affecting grain yield. The correlation of disease severity with grain yield further indicated that ergot and rust severities were causes of the significant effect on yield.