I have heard of countless reports of serious side effects from all of the toxic chemicals: fipronil (Frontline), imidacloprid (Advantage), permethrin and others including seizures, anaphylatic shock, liver and kidney damage, GI Tract complications, renal failure, and auto-immune disease... and the list goes on.
I think it is critical for everyone to remember that all of these chemicals are pesticides, regulated by the EPA in most cases, and toxic. They permeate the dog's skin, enter the bloodstream and internal organs (liver & kidney) and can filter into the intestinal tract. These chemicals are also excreted through these organs in feces and urine. The packaging provides serious warnings about not touching with your hands and washing your hands immediately after application. Hmmmm...so it is safe to pour onto your pet's skin, but you should not allow it to come into contact with your own and "keep children away".
Frontline has the lowest reported side effects and fewest claims for damages and most vets agree this one is potentially the least damaging - although none can be called safe. If you are dealing with an infestation, then one use may be necessary to break the cycle and get things under control. But otherwise, repeated use is very unhealthy for your pet and extremely dangerous for cats. There are many natural methods that are effective for repelling fleas and ticks that do not pose a health risk to the animal.