To succeed - you must start with good planning. Efforts should be focussed on reducing and simplifying the AJAX calls, and creating a standard format for responses that follows convention (ideally XML) where possible.
Follow best practice from sites such as the Open Web Application Security Project. This especially includes checking for Access Control and Input Validation flaws, whilst ensuring sensitive information travels over SSL rather than in the clear.
Never assume that Server Side AJAX checks for Access Control or User Input Validation will replace the need for final re-checking at the Server. Adding AJAX controls will never reduce your validation workload, they will only increase it.
Finally, you must be prepared to exercise a tight reign over your development team. Wonderful ideas using AJAX may sound compelling, but you should consider saving them for version 2, whilst you focus on building a rock-solid version 1.
Originally published at http://profoundway.blogspot.com/2006/06/ajax-net-security.html