The European Water Framework Directive requires the development of new and accurate methodologies, addressing the assessment of the physico-chemical status of transitional and coastal waters; these are considered by the Directive as the supporting elements for the final evaluation of the Ecological Quality Status. This contribution develops new approaches in the determination of the physico-chemical status, solving some problems detected in previous contributions, i.e.: (a) fitting the classification of water bodies and typologies, by means of the stretching of the typologies, according to the natural salinity gradient of types; (b) defining reference conditions, based upon the new approach to typologies, (c) proposing accurate multivariate methodologies, in determining the physico-chemical status of the transitional and coastal waters, based upon the defined typologies and references; and (d) discussion of the results obtained by reference to methodological aspects and water quality evolution in the Basque Country, Spain (as a case-study), during the last decade.