Water, water, everywhere… It's time to stop and think

• Six computational methods for water molecule placement and analysis reviewed alongside relevant case studies.
• Field is approaching maturity.
• Adoption into mainstream drug discovery programs will increase as more literature-based case studies are published.

Despite the numerous methods available for predicting the location and affinity of water molecules, there is still a degree of scepticism and reluctance towards using such information within a drug discovery program. Here, I review some of the most common and popular methods to assess whether these apparent concerns are justified. I suggest that the field is approaching maturity and that some methods are capable of giving quantitative predictions, which are confirmed experimentally. This suggests that water-placement methods should be used more widely to help direct chemistry efforts, although more successful examples are required to help validate the techniques.