Setting up the default program is dependent on the file type you are downloading , Ex :- PDF file will open in Adobe Reader or Acrobat.
The downloaded file will open in the default program set on your computer for that file type.
The steps may vary for Windows and Mac.
Right Click on any file with the file type you want to change the default program Ex :- Pdf ,
Select "Open With "
and in the list selct your application you want to set default Ex: Acrobat
Check the option on the bottom , "Always choose this application to open this kind of file "
Ctrl + Click on any file with the File type
Go to "Get Info"
Change the Application in the "Open With "
Select "Change All"
Close the "Get info " window
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In addition to what Manish said, you may need to edit your browsers MIME types/ file handlers. Anyway, you are not realyl providing enough info to go beyond those generic tips.