• Presents the typical chemical functionalities and fractions of asphalts. • Reviews microstructural models explaining the chemistry and rheology of asphalts. • Describes the predominant forms of molecular interactions between bitumen molecules based on the chemical functionality of the bitumen. • Explains the behavior of asphalts in terms of molecular interactions. • Collects the laboratory studies which provided some qualitative or quantitative relationships from testing evidence. Asphalt is widely used in pavement constructions where it serves as a binder to bond the aggregates together. The rheology of asphalt, which is an important consideration for selecting the proper asphalt when designing a pavement, is related to its chemical composition and microstructures. Investigating the relationships between rheology and chemistry of asphalts thus has long been a concern of researchers. This paper reviews key works from the beginning of the 20th century to the present, sorts out microstructural models that bridge asphalt chemistry and properties, and collects laboratory studies that investigated the correlation between asphalt chemical parameters and property parameters. Furthermore, the typical molecular species and corresponding molecular interactions in asphalts are also presented, whereby the rheological and phase behavior of asphalt is interpreted from the perspective of molecular interactions. This job could help researchers who are preparing for asphalt genomic studies to have a comprehensive understanding of asphalt behaviors from a chemical point of view.