Autism is a heterogeneous, behaviourally defined, neurodevelopmental condition characterised by early-emerging atypical social communication and restricted, repetitive behaviours and interests. The underlying neurocognitive underpinnings may include difficulties in social processing (particularly ‘mentalising’), executive functioning, as well as strengths in pattern recognition (attention to detail and rule-based reasoning or ‘systemising’). Each of these involves atypical brain connectivity. The underlying molecular neurobiology involves developmentally sensitive and spatiotemporally specific genetic and gene–environmental (e.g. neuroendocrine-immune) mechanisms, converging on neuronal synaptic functioning and transcriptional regulation prenatally, and their cascade effects on brain development, influenced by the autistic person’s interaction with the environmental contexts from early in life and across the lifespan. Future autism research needs to clarify the relations between the genes and the environmental factors and their relations to neurocognitive architectures, to identify factors associated with plasticity in developmental trajectories and to develop neurobiologically informed therapeutics and support strategies that are precisely tailored to respect individual differences.