Yes, skin can develop a tolerance against specific products if they are used long enough. This is an especially common situation for individuals that suffer from acne breakouts. If you have been using a product for a while and are starting to notice that it is no longer working I would recommend discussing other options with your dermatologist or trying a different brand that will meet your skin needs. I just recently had to start using a new blemish fighting treatment, as my skin has developed an immunity against my old blemish moisturizer. Hope this helps!