Wastewater-based epidemiology (WBE) has been employed by many countries globally since the beginning of the COVID-19 pandemic in order to assess the benefits of this surveillance tool in the context of informing public health measures. WBE has been successfully employed to detect SARS-CoV-2 at wastewater treatment plants for community-wide surveillance, as well as in smaller catchments and institutions for targeted surveillance of COVID-19. In addition, WBE has been successfully used to detect new variants, identify areas of high infection levels, as well as to detect new infection outbreaks. However, due to to the large number of inherent uncertainties in the WBE process, including the inherent intricacies of the sewer network, decay of the virus en route to a monitoring point, levels of recovery from sampling and quantification methods, levels of faecal shedding among the infected population, as well as population normalisation methods, the usefulness of wastewater samples as a means of accurately quantifying SARS-CoV-2 infection levels among a population remains less clear. The current WBE programmes in place globally will help to identify new areas of research aimed at reducing the levels of uncertainty in the WBE process, thus improving WBE as a public health monitoring tool for future pandemics. In the meantime, such programmes can provide valuable comparisons to clinical testing data and other public health metrics, as well being an effective early warning tool for new variants and new infection outbreaks. This review includes a case study of sampled wastewater from the sewer network in Dublin, Ireland, during a peak infection period of COVID-19 in the city, which evaluates the different uncertainties in the WBE process.