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Seasonality, a systematic periodic occurrence of events over the course of a year, is a well-known phenomenon in life and health sciences. Understanding seasonal fluctuations in diseases patterns presents us with major analytical challenges. In the modern view, the key determinants of temporal variations in disease manifestation are evolving host susceptibility, periodicity in pathogen abundance and transmissibility, and the ever-changing environment that can support or repress a host or pathogen. To develop efficient strategies for disease prevention, treatment, and control, we need to grasp the main determinants of temporal variations and their interactions. This presentation introduces the notion of seasonality, using as illustrations respiratory and enteric infections. I will demonstrate the use of novel datastreams originated in the fields of molecular biology and immunogenetics that guide our understanding of the nature of diseases’ seasonality.