The water content of six different substances was determined by means of five different methods. The methods used were loss on drying, thermogravimetry (coupled with DSC), a new phosphorous-pentoxide method, direct Karl-Fischer titration and the Karl-Fischer oven. A combination of direct Karl-Fischer titration and the KF-oven method was found to be the optimal technique for water determination of substances of unidentified chemical and thermal behaviour based on detailed considerations about selectivity, type of water binding, sample properties and efficiency.