Anaerobic process modelling is a mature and well-established field, largely guided by a mechanistic model structure that is defined by our understanding of underlying processes. This led to publication of the IWA ADM1, and strong supporting, analytical, and extension research in the 15 years since its publication. However, the field is rapidly expanding, in terms of new technology, new processes, and the need to consider anaerobic processes in a much broader context of the wastewater cycle as a whole. Within the area of technologies, new processes are emerging (including high-solids and domestic wastewater treatment). Challenges relating to these new processes, as well as the need to intensify and better operate existing processes have increased the need to consider spatial variance, and improve characterisation of inputs. Emerging microbial processes are challenging our understanding of the role of the central carbon catabolic metabolism in anaerobic digestion, with an increased importance of phosphorous, sulfur, and metals as electron source and sink, and consideration of hydrogen and methane as potential electron sources. The paradigm of anaerobic digestion is challenged by anoxygenic phototrophism, where energy is relatively cheap, but electron transfer is expensive. These new processes are commonly not compatible with the existing structure of anaerobic digestion models. These core issues extend to application of anaerobic digestion in domestic plant-wide modelling, with the need for improved characterisation, new technologies having an increased impact, and a key role for the linked phosphorous–sulfur–iron processes across the cycle. The review overall finds that anaerobic modelling is increasing in complexity and demands on the modeller, but the core principles of biochemical and physicochemical processes, metabolic conservation, and mechanistic understanding will serve well to address the new challenges.