Septoria leaf spot, caused by the fungus Septoria albopunctata, is a disease of increasing concern to the blueberry industry in Georgia and other southeastern states. Due to critical gaps in knowledge on disease ecology and epidemiology, current disease management guidelines are highly empirical. With this in mind, a series of field studies was carried out from 2001 to 2004 to generate key epidemiological information on temporal disease progression, seasonal inoculum dynamics, and the effects of disease on premature defoliation and yield. Additional studies were carried out to develop improved disease assessment and sampling procedures. Disease onset on rabbiteye blueberries grown near Athens was observed between late April and mid-June, and disease severity increased rapidly and reached a maximum by mid- to late September; thereafter, disease severity decreased until the end of the season. Disease severity was highest on early-emerging leaves and on leaves located on shoots closer to the ground. Pycnidiospore inoculum was present throughout the season, and leaves became infected by S. albopunctata season-long. Disease severity, defoliation, flower bud set, and return yield were found to be interrelated. Leaves with high disease severity at harvest abscised earlier in the fall than leaves with low disease severity, and shoots with severely diseased leaves and/or high levels of defoliation had a reduced potential to set flower buds. Furthermore, such shoots consistently had low return yields the following year. These results form the basis for identifying specific disease severity or defoliation levels that can be tolerated during specific periods of crop development without negatively impacting flower bud set and return yield. Based on the data collected in this multi-year field study, hierarchical sampling plans were developed for assessing disease severity and defoliation; these plans will be useful for obtaining reliable estimates of the two variables with the least expenditure of time.