It can be challenging to determine which whole genome sequencing clusters should be investigated, and once investigations are initiated, how aggressively they should be pursued. Epidemiologists have to balance preserving limited public health resources by minimizing investigations of clusters that are less likely to have a common source, with the goal of identifying as many outbreaks as possible as soon as possible. Here are some key points for determining how to prioritize Salmonella and STEC WGS clusters for investigation and how hard to pursue them, based on Minnesota Department of Health’s (MDH) experience and the peer-reviewed literature.