Depends on what you're testing...
ISEMPTY is for testing if a variable has a value assigned to it...
If a value has been assigned to the variable (even a value of "") then it is NOT empty. If no value has been assigned to the variable, it IS Empty.
If you use ISEMPTY to test a RANGE, it works the same as ISBLANK.
IsBlank and ="" should be used to test if a RANGE is blank.
="" will count Forumula Blanks as blank, where IsBlank will not. IsBlank will consider a formula blank as NOT blank.
Hope that clears up a little..