To understand its unprecedented resurgence, we examined the epidemiological, virological, and entomological features of dengue in Guangzhou during 1978–2009. Cases reported to the Guangzhou Centre for Disease Control and Prevention and data from virological and entomological surveillance were analyzed from three periods: 1978–1988, 1989–1999, and 2000–2009. Although cases decreased over time: 6,649 (1978–1988) to 6,479 (1989–1999) to 2,526 (2000–2009), geographical expansion resulted in districts with an average incidence >2.5/100,000, increasing from five (1978–1988, 1989–1999) to seven (2000–2009). Age distribution (mean age: 34.9 years) provided a trend of increasing dengue incidence among adults, and there was a significantly higher incidence among men with a sex ratio of 1.15:1 (P<0.001). Cases occurred from May through November with a peak between August and October, and a long-term trend was characterized by a three to five-year cyclical pattern. The most frequently isolated serotypes were DENV-2 (1978–1988) and DENV-1 (1989–1999 and 2000–2009). Seasonal fluctuations in immature densities of Aedes albopictus (sole transmission vector in Guangzhou) were consistent with the dengue seasonality. After a 30-year apparent absence, DENV-3 had reemerged in 2009. The current epidemiological situation is highly conducive to periodic dengue resurgences. Thus, a high degree of surveillance and strict control measures in source reduction should be maintained.