The challenge of disentangling political communication processes and their effects has grown with the complexity of the new political information environment. But so have scientists’ toolsets and capacities to better study and understand them. We map the challenges and opportunities of developing, synthesizing, and applying data collection and analysis techniques relying primarily on computational methods and tools to answer substantive theory-driven questions in the field of political communication. We foreground the theoretical, empirical, and institutional opportunities and challenges of Computational Communication Science (CCS) that are relevant to the political communication community. We also assess understandings of CCS and highlight challenges associated with data and resource requirements, as well as those connected with the theory and semantics of digital signals. With an eye to existing practices, we elaborate on the key role of infrastructures, academic institutions, ethics, and training in computational methods. Finally, we present the six full articles and two forum contributions of this special issue illustrating methodological innovation, as well as the theoretical, practical, and institutional relevance and challenges for realizing the potential of computational methods in political communication.