That one is quite simple.
As you know, you get a "sureshot" if you have twice or more the attack of your opponent.
Hence, in a round with 2 cards with equals powers, if you put one pillz when your opponent doesnt put anything: you get a sureshot At the cost of only 1 pillz, it's worth it, no?
This one pillz can be very powerfull
*and to add..putting only one pill or few pillz ensures you victory in the end if your opponent wastes most of his/her pillz..specially if you're in a no random room..a pill will usually either force an opponent put one pill or more than one pill just to beat your card..so in a way..you are ensured that you will have more pillz than your opponent in the end..
*putting one pill in a no random room can be beneficial sometimes..some people just let first round cards through because they are playing things safe..so sometimes..your card will win because your opponent didn't use a pill on his/hers..
*so either playing offensive or defensive..putting just one pill or a few pillz is one of the safest ways to play..
And to further add...
at equal power: putting 1 single pill in (in addition to the 1 free) makes your opponent need to use 3 (three) pillz to get sureshot, else you still have chance of winning.
As said, the first pill (sometimes 2 or 3) has (mostly) an excellent cost/benefit equation...even if it sometimes just does not work out.
This is all under the assumption that the cards in question are completely equal. In practice, that rarely happens. For example, say that you had a hand with 4 Uppers, while your opponent had a hand of 4 GHEIST. Now, GHEIST isn't known for high power, nor do they have a good bonus. So if you played, say, Zatman, the opposing player would most likely either let him through, or spend lots of pills to beat him, seeing as a six power card would need at least two pills to have a decent chance of winning against a zero pill card with 8 power and -10 opp attack.