At the core of geographic information science (GIScience) lie enduring organising principles and concepts that have been developed using research methods that are robust, transparent and scientifically reproducible. Yet it is also a science of real-world problem solving, which has come to prominence at a time in which the nature and volume of geographic information (and the human activities that generate it) are profoundly changing. This article assesses and interprets these changes in the context of Goodchild's assessment of challenges to GIScience, using examples from 'geodemographics' - the analysis of people according the places where they live. The conclusions have repercussions not only for the way that we think about neighbourhood profiling, but also for the practice of GIScience itself, specifically with regard to reconciling new sources of 'big' spatial data and understanding the inherent vagaries of citizen science; linkage of conventional social, economic and demographic geographies to patterns of virtual interactions at fine levels of spatial granularity; and improving understanding of the ways in which 'open' geodemographics are specified, estimated and tested.