As you play Clue, you will gather clues that will help you to determine the suspect, weapon, and location of the murder. To keep track of the clues you collect, you should keep good notes and include the initials of the players who have each of the clues you collect. Doing so will help you to get closer to the truth and win the game. Make sure that you check off clues on your detective's notes sheet or write them on your notepad as you collect them. Your opponents will also be searching for clues to solve the murder, so it is a good idea to pay attention to their suggestions. Just keep in mind that they may try to throw you off sometimes, so be careful not to consider all of their suggestions as clues. If another player shows them a card, secretly watch where the first person writes the X down on the paper. If he writes it low on the sheet of paper, it is a room. If he writes it at the top, it means he was shown either a weapon or a character. Try to become familiar with the layout of the detective's notes sheet so that it is easier for you to tell what your opponents are marking off. Try flipping your sheet upside down to throw off other players who may be watching you as well. If a card keeps getting suggested and no one seems to have it, then it may be in the envelope. Make a note of it on your detective's notes sheet, but try not to be obvious about it. Write it down a little after the name suspect, weapon, or room was mentioned.
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One-sentence summary -- Keep good notes on the clues you collect. Pay attention to the suggestions other players make. Watch other players as they check items off on their lists. Pay attention to what card names are being said over and over.

When starting the game, you will be able to choose a few upgrades for your virus. What you choose here will have a huge impact on how the game plays out, so choose wisely. There are a few suggested upgrades that you should pick to make this game easier: DNA Gene - ATP Boost. This will give you extra DNA points at the beginning. Travel Gene - Aquacyte. Basically required to infect difficult islands like Greenland, Iceland, and New Zealand. Evolution Gene - Patho-Stasis. This will make your upgrades much cheaper. Mutation Gene - Genetic Mimic. This slows the cure progression, offsetting the negative effects of the Patho-Stasis upgrade. Environment Gene - Extremophile. This boosts the infection rate in every environmental condition. Before choosing a starting country, use your ATP Boost bonus to purchase a few starting upgrades. These upgrades will increase ineffectiveness while keeping lethal mutations from showing up too early. Coughing Gene Compression 1 and 2 Your starting country is very important, as this will determine how quickly the virus starts spreading. Most guides recommend starting in India due to the large population and proximity to China, though others suggest Saudi Arabia. Work will begin on the cure shortly after the game begins.
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One-sentence summary --
Choose your genes. Buy some initial upgrades. Choose a starting country.