This answer is hard to answer because I really feel it's strongly based on your 
development style. Are you an old CF 5 developer that's just getting into the 
MX arena (or maybe you're still not there)? - Fusebox is a wonderful framework 
for these folks. Are you an OOP junkie? - Mach-II might be your answer. Are you 
a developer who heavily relies on CFCs but doesn't really care for the OOP 
approach? - model-glue might be your answer. 

Now the real cool thing out there in the coldfusion development architecture 
world are ORMs - the front runners here are Transfer and Reactor. In my 
experience recently, Transfer is knocking the socks off of Reactor and has been 
a much more active open source project than Reactor. However, both work 
extremely well. If you haven't used an ORM yet, you definitely need to try one 
out :). For those of you not "in the know", ORM stands for "object role 
modeling" (fancy term, whatever) - the basic idea is that you tell the ORM a 
few little details about your database tables (what's the table name, what's 
the PK, what's the relation between your tables) which is typically done in 
XML. From there, it creates all of your select, insert, update, delete 
functionality (Commonly called CRUD operations) for you :). Any developer who 
has done a fair sized project will know that these functions take a good third 
of your development time - when this gets taken care of for you it is HUGE. 

So to answer your question, choosing a framework really depends on development 
style and in many cases choosing multiple "frameworks" may make a winning 
combination. Please note that the term "frameworks" is being used very loosely 
here - Fusebox and Model glue basically have the same use; transfer and reactor 
basically have the same use. A winning combination may be model glue and 
reactor (and coldspring for the model-glue unity setup) or fusebox and 
transfer. 

Get your nose out there, and give these frameworks a try!

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