The concentrations of trace elements (TEs) in large boreal rivers can fluctuate markedly due to changing water levels and flow rates associated with spring melt and variable contributions from tributaries and groundwaters, themselves having different compositions. These fluctuating and frequently high concentrations create regulatory challenges for protecting aquatic life. For example, water quality criteria do not account for changes in flow regimes that can result in TE levels that may exceed regulatory limits, and neither do they account for the markedly different lability and bioaccessibility of suspended solids. This review addresses the geochemical and biological processes that govern the lability and bioaccessibility of TEs in boreal rivers, with an emphasis on the challenges posed by the colloidal behaviour of many TEs, and their relationship to the dissolved fraction (i.e., <0.45 μm in size). After reviewing the processes and dynamics that give rise to the forms and behaviour of TEs in large boreal rivers, their relevance for aquatic organisms and the associated relationships between size and lability and bioaccessibility are discussed. The importance of biological variables and different forms of TEs for limiting lability and bioaccessibility are also addressed. Two case studies emphasize seasonal fluctuations and accompanying changes in the distribution of TE amongst different size fractions and associated colloidal species in large boreal rivers: the Northern Dvina and one of its tributaries, the Pinega River, both in Russia, and the Athabasca River in Alberta, Canada. Water quality in the Athabasca River is briefly discussed with respect to Canadian guidelines.