AbstractAfter a year of living with the COVID-19 pandemic and its associated consequences, hope looms on the horizon thanks to vaccines. The question is what percentage of the population needs to be immune to reach herd immunity, that is to avoid future outbreaks. The answer depends on the basic reproductive number, R0, a key epidemiological parameter measuring the transmission capacity of a disease. In addition to the virus itself, R0 also depends on the characteristics of the population and their environment. Additionally, the estimate of R0 depends on the methodology used, the accuracy of data and the generation time distribution. This study aims to reflect on the difficulties surrounding R0 estimation, and provides Spain with a threshold for herd immunity, for which we considered the different combinations of all the factors that affect the R0 of the Spanish population. Estimates of R0 range from 1.39 to 3.10 for the ancestral SARS-CoV-2 variant, with the largest differences produced by the method chosen to estimate R0. With these values, the herd immunity threshold (HIT) ranges from 28.1 to 67.7%, which would have made 70% a realistic upper bound for Spain. However, the imposition of the delta variant (B.1.617.2 lineage) in late summer 2021 may have expanded the range of R0 to 4.02–8.96 and pushed the upper bound of the HIT to 90%.