One of the problems preventing the widespread commercialization of ISFETs is the lack of reliable packaging. The most important parameter in the packaging is the interface adhesion between the encapsulant and the chip. This interface is characterized by two independent types of measurements. Long-term C-V measurements are used to check the water penetration along the interface. CO2 and NH3 response measurements are used to show the existence of condensed water at the interface. It is shown that the use of a suitable coupling agent improves the adhesion. However, vacuoles at the interface can still be formed and these can cause a breakdown of the packaging. The use of thicker layers of encapsulant will only postpone this breakdown.