Some things are very hard to backtest, like the workings of the queues in the order book... with enough book feeds data and some creative logic you can get a good approximation but it is very difficult to get it right and it'll never be perfect. Other things like the impact of your orders in the market price are simply impossible to simulate.
This means that strategies that rely heavily in market microstructure, liquidity constraints and the latency race would be very difficult or even impossible to backtest... but this doesn't stop the HFT crowd from deploying systems that mostly fall on this space.