Cell function relies on the coordinated action of heterogeneous interconnected networks of biomolecules. Mathematical models help us explore the dynamics and behaviour of these intracellular networks in greater detail. Models of increasing scale and complexity are being developed to probe cellular processes, often necessitating the use of several types of mathematical representation in hybrid models. Here we review recent efforts to incorporate the influences of stochasticity and spatial heterogeneity into cellular level models, ranging from abstract coarse-grained representations to large-scale hybrid models comprising thousands of biological components. We discuss the key challenges involved in, and recent mathematical advances enabling the development and analysis of mathematical models of complex intracellular processes.