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>When using DEFINE statements inside an INCLUDE file must one use the #INCLUDE statement in every program that references the DEFINE's?

Yes

> What about forms? Must one use a #INCLUDE in every method/event of a form which may reference a DEFINE in the INCLUDE file or is there an easier global way to specify the INCLUDE file for the entire application?

You can specify #INCLUDE file for a form in the Form/Class Designer in the Form/Class -> Include menu. The file specifie in the _INCLUDE system variable will be used for any new form/class but there's no global runtime include file for an application.